The interactions of proteins with DNA, RNA, other proteins, or small molecules are central to all biological processes. Indeed, important biological processes, such as viral infections or immune cell destruction of pathogens, are consequences of a series of specific molecular interactions. Analysis of interactions between isolated macromolecules and a detailed dissection of molecular interfaces is key to understanding many biological processes. In combination with recombinant DNA technology to generate and modify proteins, and high resolution methods to visualize atomic structures of biomolecules, biosensor-based functional assays are becoming essential tools to probe protein-protein and protein-ligand interactions. A commercially available system called the BIAcore uses biosensor-based technology for monitoring biomolecular interactions. For example, to study interactions between two protein molecules, one protein is immobilized on a sensor surface and the second protein is injected over the surface. Detection of binding is based upon the optical phenomenon of surface plasmon resonance, which relates to mass changes and consequent refractive index changes at the sensor chip surface. The BIAcore device can be used to obtain information about the kinetics, affinity and specificity of macromolecular interactions. Other applications for this technology include binding site analyses, delineating specific interacting molecules within complex systems, fractional of impure samples to identify components with a specified binding activity, and establishing rapid assays for monoclonal antibody and drug screening. The University of Michigan does not currently have a BIAcore machine in any of the Ann Arbor campuses. Funds are requested to obtain a BIAcore instrument at the University of Michigan under the NCRR Shared Instrumentation Grant Program. The instrument will be used by a number of investigators from six different departments at the University for a variety of applications outlined in this proposal. The availability of a BIAcore at the University of Michigan will greatly strengthen the ability of the investigators to address problems currently under study by permitting the measurement of molecular interactions.